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Xenotransplantation

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Cell transplants some success (porcine islet cells) Shortfall in ... PERVS (porcine endogenous retroviruses), can infect human cells in vitro and mice in vivo. ... – PowerPoint PPT presentation

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Title: Xenotransplantation


1
Xenotransplantation
  • Transplant of organs/tissues from one animal
    species into another

2
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3
Types of transplants
  • Autograft (self to self)
  • Isograft (from genetically identical individual)
  • Allograft (from genetically non-identical member
    of same species)
  • Xenograft (from one species to another)

4
Concerns with xenografts
  • Hyperacute rejection
  • Later immunological problems
  • Risks, especially infectious
  • Ethical issues
  • Use of animals, especially GM
  • Creation of new transmissible disease

5
Xenotransplantation
  • History
  • Blood transfusions in early 17thC
  • Solid organ transplants in 20thC (chimpanzee
    kidney, use of immunosuppression, failure with
    other species as donors)
  • Cell transplants some success (porcine islet
    cells)
  • Shortfall in supply (UK figures for 2001)
  • Waiting list 6842
  • Donors 777
  • Transplants 2339
  • Shortfall 4503

6
Potential donor species
  • Chimpanzee
  • Pigs
  • Appropriate size
  • Already bred for slaughter
  • Extensive knowledge of husbandry and infectious
    diseases
  • Transgenic and knockout pigs available
  • Phylogenetic distance reduces risk of infectious
    diseases

7
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8
Potential donor species
  • Lifespan differences?
  • Continuing growth of organs from young donors?
  • Cross species compatibility of produced hormones
    (insulin, renin?, erythropoietin?)
  • Body temperature (37º versus 39º)

9
Associated problems
  • Hyperacute rejection
  • Xenoreactive natural antibodies in recipient
    against the gal epitope on cells of non-primate
    species
  • Generated in response to gut microbes that have
    epitope on surface
  • Act by complement activation and NK cells
  • Later immunological problems
  • Acute (24hrs) rejection due to IgM and IgG
    anti-gal leading to DIC
  • CMI rejection

10
Associated problems
  • Risks
  • Infectious agents
  • PERVS (porcine endogenous retroviruses), can
    infect human cells in vitro and mice in vivo.
  • Theoretical generation of pathogenic,
    replication- competent, exogenous retrovirus
  • Assessing and reducing the risk
  • Long history of using porcine heart valves and
    insulin
  • Eliminate known agents from donor herd
  • No PERV transmission in 160 pig cell recipients

11
Ethical issues
  • Producing Frankenstein creatures
  • Choice of donor species (Speciesism)
  • Health and welfare of donors (particularly GM
    donors)
  • Risk of generating new infectious pathogen
    (save individual but risk mankind)
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